旱生香茶菜总二萜包合物对小鼠移植性肿瘤的抗肿瘤活性及其毒性研究  

Antitumor activities and toxicities of the total diterpenoids of Isodon Xerophilus inclusion complex on mouse transplanted tumor

作　　者：杨焕芝[1,2] 周轶平[2] 翁稚颖[2] 罗敏[2] 孙汉董[3] 李玛琳[4,2] 

机构地区：[1]昆明市第一人民医院药学部,昆明650011 [2]昆明医科大学药学院暨云南省天然药物药理重点实验室,昆明650500 [3]中国科学院昆明植物研究所,昆明650204 [4]云南中医学院,昆明650500

出　　处：《中国临床药理学杂志》2016年第19期1785-1788,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究旱生香茶菜总二萜包合物(IXD)对小鼠移植性肿瘤的抗肿瘤活性及其毒性。方法急性毒性实验:1ICR小鼠20只,雌雄各半,按体重随机分为5组(每组4只):正常对照组(蒸馏水),4个剂量(150,100,70,40mg·kg-1)IXD包合物组,一次性腹腔注射,测定IXD包合物LD50。2ICR小鼠20只,雌雄各半,一次性灌胃IXD包合物500 mg·kg-1,测定IXD包合物最大耐受剂量(MTD)。3ICR小鼠18只,雌雄各半,按体重随机分为6组(每组3只):正常对照组(蒸馏水),5个剂量(普朗尼克,2.95,4.53,6.97,10.73,16.5g·kg-1)辅料组,一次性经灌胃给药。这3种情况均连续给药7 d,观察小鼠的呼吸、胃肠、心血管、生殖、皮肤、毛发及行为等,记录小鼠的毒性反应和死亡情况。抗肿瘤活性实验:以ICR小鼠制备成S180肉瘤小鼠模型,按照体重随机分为7组(每组10只):低、中、高3个剂量(30,60,120 mg·kg-1·d^(-1))IXD包合物组、辅料对照组(普朗尼克3960 mg·kg-1·d^(-1))、溶剂对照组(蒸馏水)、阳性对照组(环磷酰胺30 mg·kg-1·d^(-1))和阴性对照组(生理盐水),经灌胃连续给药7 d后,测定肉瘤重量、体重及对主要脏器的影响。结果小鼠经腹腔注射IXD的半数致死量(LD50)为113.14 mg·kg-1,经灌胃MTD>500 mg·kg-1。与溶剂对照组相比,3个剂量MTD组对荷S180肉瘤小鼠抑瘤率分别为18.16%,34.69%,54.45%,中、高2个剂量差异有统计学意义(均P<0.05);中、高2个剂量MTD和辅料对照组小鼠肾指数分别减少9.14%,9.99%,10.21%,差异有统计学意义(均P<0.05);但是对荷瘤小鼠体重、肝、脾、胸腺及心脏无明显影响。结论 MTD毒性低,对S180肉瘤的生长有明显的抑制作用。Objective To study the antitumor activity and acute toxicity of the total diterpenoids of Isodon Xerophilus（IXD） inclusion complex on mouse transplanted tumor.Methods Acute toxicity experiment：1Twenty ICR mice were half male and female respectively,according to the weight were randomly divided into 5 groups（4 mice in each group） ：normal control group（distilled water）,four doses（150,100,70,40mg·kg-1） IXD inclusion complex group,IXD inclusion complex were intraperitoneal injection one-time to determine the LD50.2Twenty ICR mice were half male and female respectively,500 mg·kg-1IXD inclusion complex was intragastricly one-time administered to measure the maximum tolerated dose（MTD） in mouse.3 Eighteen ICR mice werehalf male and female respectively,according to the weight were randomly divided into 6 groups（3 mice in each group） ：normal control group（distilled water）,five doses（2.95,4.53,6.97,10.73,16.5 g·kg-1Pluronic F68） ingredient control group was ig administered one-time to measure the toxicity of Pluronic F68 in mouse.The three conditions were all observed the respiratory,gastrointestinal,cardiovascular,reproductive,skin,hair and behavior and recorded the toxicity reaction of mice and death for continuous 7 days.Antitumor activity experiment：Take 70 ICR mice to prepare S180 tumor models and divided these into 7 groups（10 mice in each group） ：the low,medium and high dose groups of IXD inclusion complex（30,60,120 mg·kg-1·d^（-1））,ingredient control group（3960 mg·kg-1·d^（-1）Pluronic F68）,solvent control（distilled water group）,positive control group（30 mg · kg-1· d-1cyclophosphamide）,negative control（saline group）.IXD inclusion complex were ig administered to mice with transplanted sarcoma（S180） for consecutive 7 days and to observe their influence on tumor＇s weight,mouse＇s weight and main organs.Results Through ip administration,LD50 in mouse for the complex was 113.14 mg·kg-1,the MTD 500 mg·kg-1.Compared with the solvent c

关 键 词：旱生香茶菜总二萜包合物 急性毒性 小鼠移植性肿瘤 抗肿瘤活性 

分 类 号：R28[医药卫生—中药学]